Efficacy and safety of sugarcane policosanol on dyslipidemia: A meta-analysis of randomized controlled trials.
This study aimed to systematically investigate whether sugarcane policosanol was effective and safe on dyslipidemia. A total of 11 databases including the PubMed, Web of science, Embase, Scopus, the Cochrane library and SinoMed databases were searched for available studies investigating the effects of policosanol on dyslipidemia. A total of 22 studies including 1886 subjects were included in the analysis. The pooled results showed that compared with placebo, sugarcane policosanol could significantly reduce total cholesterol (TC, 95% CI: -0.87 to -0.30 mmol/L) and low density lipoprotein cholesterol (LDL-c, 95% CI: -1.02 to -0.40 mmol/L) and increase high density lipoprotein cholesterol; however, no significant effects were observed on triglyceride (TG) and body weight. Subgroup analysis suggested the studies from Cuba obtained more effective data than those outside this country, and the effects were not proportional to the dose. The adverse effects analysis demonstrated that sugarcane policosanol was safer than the control agents. The pooled results supported the lipid-lowering effects and safety of policosanol. Because of the high heterogeneity, the better treatment effects observed in the Cuban studies and the inconsistent dose-response relationship, more clinical trials are needed to further confirm the efficacy of policosanol on dyslipidemia.


Clinical outcome of henipavirus infection in hamsters is determined by the route and dose of infection.
Nipah virus (NiV) and Hendra virus (HeV) are emerging zoonotic viruses and the causative agents of severe respiratory disease and encephalitis in humans. Little is known about the mechanisms that govern the development of respiratory and neurological disease. Using a hamster model of lethal NiV and HeV infection, we describe the role of the route and dose of infection on the clinical outcome and determine virus tropism and host responses following infection. Infection of hamster with a high dose of NiV or HeV resulted in acute respiratory distress. NiV initially replicated in the upper respiratory tract epithelium, whereas HeV initiated infection primarily in the interstitium. In contrast, infection with a low dose of NiV or HeV resulted in the development of neurological signs and more systemic spread of the virus through involvement of the endothelium. The development of neurological signs coincided with disruption of the blood-brain barrier (BBB) and expression of tumor necrosis alpha (TNF-α) and interleukin 1 β (IL-1β). In addition, interferon-inducible protein 10 (IP-10) was identified as playing an important role in NiV and HeV pathogenesis. These studies reveal novel information on the development and progression of NiV and HeV clinical disease, provide a mechanism for the differences in transmission observed between NiV and HeV outbreaks, and identify specific cytokines and chemokines that serve as important targets for treatment.


Caste-biases in gene expression are specific to developmental stage in the ant Formica exsecta.
Understanding how a single genome creates and maintains distinct phenotypes is a central goal in evolutionary biology. Social insects are a striking example of co-opted genetic backgrounds giving rise to dramatically different phenotypes, such as queen and worker castes. A conserved set of molecular pathways, previously envisioned as a set of 'toolkit' genes, has been hypothesized to underlie queen and worker phenotypes in independently evolved social insect lineages. Here, we investigated the toolkit from a developmental point of view, using RNA-Seq to compare caste-biased gene expression patterns across three life stages (pupae, emerging adult and old adult) and two female castes (queens and workers) in the ant Formica exsecta. We found that the number of genes with caste-biased expression increases dramatically from pupal to old adult stages. This result suggests that phenotypic differences between queens and workers at the pupal stage may derive from a relatively low number of caste-biased genes, compared to higher number of genes required to maintain caste differences at the adult stage. Gene expression patterns were more similar among castes within developmental stages than within castes despite the extensive phenotypic differences between queens and workers. Caste-biased expression was highly variable among life stages at the level of single genes, but more consistent when gene functions (gene ontology terms) were investigated. Finally, we found that a large part of putative toolkit genes were caste-biased at least in some life stages in F. exsecta, and the caste-biases, but not their direction, were more often shared between F. exsecta and other ant species than between F. exsecta and bees. Our results indicate that gene expression should be examined across several developmental stages to fully reveal the genetic basis of polyphenisms.


Exploring potential prejudice toward older adult mobility device users.
Many older adults require assistive technology to maintain mobility (e.g., canes, walkers, wheelchairs, or scooters), but concerns about experiencing prejudice because of mobility devices can deter use. We explore this potential prejudice in a sample recruited through online crowdsourcing. Overall, prejudice toward older adult mobility device users was not observed. Older adult mobility device users were evaluated more positively than common prejudice target groups. However, heightened prejudice toward older adult mobility device users was observed among those higher in authoritarianism or social dominance orientation. This was explained by perceptions that older adult mobility device users are a greater threat to resources (e.g., health care spending, time, attention) among those higher in these qualities. This pattern was present at all ages assessed but was stronger for those who were younger versus older. Relationships between ideology and heightened threat from older adult mobility device users were not present for those older than 60 years of age. Our results demonstrate that concerns about this prejudice are not completely unwarranted. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Deoxyguanosine kinase deficiency presenting as neonatal hemochromatosis.
Mutations in DGUOK result in mitochondrial DNA (mtDNA) depletion and may present as neonatal liver failure. Neonatal hemochromatosis (NH(1)) is a liver disorder of uncertain and varied etiology characterized by hepatic and non-reticuloendothelial siderosis. To date, deoxyguanosine kinase (dGK(2)) deficiency has not been formally recognized in cases of NH. We report an African American female neonate with clinical and autopsy findings consistent with NH, and mtDNA depletion due to a homozygous mutation in DGUOK. This report highlights hepatocerebral mtDNA depletion in the differential of neonatal tyrosinemia, advocates considering dGK deficiency in cases of NH, and posits mitochondrial oxidative processes in the pathogenesis of NH.


The endoplasmic reticulum binding protein BiP displays dual function in modulating cell death events.
The binding protein (BiP) has been demonstrated to participate in innate immunity and attenuate endoplasmic reticulum- and osmotic stress-induced cell death. Here, we employed transgenic plants with manipulated levels of BiP to assess whether BiP also controlled developmental and hypersensitive programmed cell death (PCD). Under normal conditions, the BiP-induced transcriptome revealed a robust down-regulation of developmental PCD genes and an up-regulation of the genes involved in hypersensitive PCD triggered by nonhost-pathogen interactions. Accordingly, the BiP-overexpressing line displayed delayed leaf senescence under normal conditions and accelerated hypersensitive response triggered by Pseudomonas syringae pv tomato in soybean (Glycine max) and tobacco (Nicotiana tabacum), as monitored by measuring hallmarks of PCD in plants. The BiP-mediated delay of leaf senescence correlated with the attenuation of N-rich protein (NRP)-mediated cell death signaling and the inhibition of the senescence-associated activation of the unfolded protein response (UPR). By contrast, under biological activation of salicylic acid (SA) signaling and hypersensitive PCD, BiP overexpression further induced NRP-mediated cell death signaling and antagonistically inhibited the UPR. Thus, the SA-mediated induction of NRP cell death signaling occurs via a pathway distinct from UPR. Our data indicate that during the hypersensitive PCD, BiP positively regulates the NRP cell death signaling through a yet undefined mechanism that is activated by SA signaling and related to ER functioning. By contrast, BiP's negative regulation of leaf senescence may be linked to its capacity to attenuate the UPR activation and NRP cell death signaling. Therefore, BiP can function either as a negative or positive modulator of PCD events.


Lack of association between the rs2294008 polymorphism in the prostate stem cell antigen gene and colorectal neoplasia: a case-control and immunohistochemical study.
Prostate stem cell antigen (PSCA) has been implicated in the pathogenesis of several solid tumours, either due to changes in protein expression, or through association with the rs2294008 polymorphism in the PSCA gene. To our knowledge, the role of PSCA in the development of colorectal neoplasia has not been explored. We performed a genotyping study to assess for associations between the rs2294008 polymorphism and risk of adenomatous polyps and colorectal cancer. DNA samples were available from 388 individuals with colorectal neoplasia and 496 controls, all of whom had undergone screening colonoscopy. In addition, we performed immunohistochemical staining for PSCA in colonic tissue representing all stages of the adenoma-carcinoma sequence. No genotypic associations were found between the rs2294008 polymorphism and the risk of colorectal adenomata or cancer. Immunohistochemical staining did not reveal any alteration in PSCA expression accompanying the adenoma-carcinoma sequence. From these data it seems unlikely that PSCA has a role in the initiation or progression of colorectal neoplasia.


Glycine metabolism in rat kidney cortex slices.
When rat kidney cortex slices were incubated with glycine or [1-14C]glycine, after correcting for metabolite changes with control slices, product formation and glycine utilization fitted the requirements of the equation: 2 Glycine leads to ammonia + CO2 + serine. Evidence is presented that degradation via glyoxylate, by oxidation or transamination, is unlikely to have any significant role in kidney glycine catabolism. It is concluded that glycine metabolism in rat kidney is largely via glycine cleavage closely coupled with serine formation. 1-C decarboxylation and urea formation with glycine in rat hepatocyte suspensions were somewhat greater than decarboxylation or ammonia formation in kidney slices, showing that in the rat, potentially, the liver is quantitatively the more important organ in glycine catabolism. There was no evidence of ammonia formation from glycine with rat brain cortex, heart, spleen or diaphragm and 1-C decarboxylation was very weak.


Cephalic Rotation of the Nasal Tip.
The position of the nasal tip holds important aesthetic significance. Cephalic rotation of the nasal tip is a frequent motivating factor for patients seeking rhinoplasty. The position of the nasal tip is a complex interplay of the size, morphology, and position of several anatomical components of the lower one-third of the nose. Cephalic rotation can be achieved by means of six different methods. The indirect methods promote passive cephalic rotation and include cephalic trim of the lower lateral cartilages, caudal trim of the upper lateral cartilages, and caudal septal trim. Direct methods involve precise repositioning of the domes and include shortening the lateral crura, lateral domal relocation, and the tip rotation suture. Used alone or in combination, these techniques and their subtle variations represent comprehensive and effective methods to achieve cephalic rotation of the nasal tip.


Ventricular tachycardia in nonischemic cardiomyopathy: Anteroseptal vs inferolateral origin based on ICD ventricular electrogram timing.
The majority of patients with nonischemic cardiomyopathy (NICM) present a perivalvular substrate that is either predominantly antero-septal (AS) or infero-lateral (IL), corresponding to specific ventricular tachycardia (VT) morphologies. The relative timing of far-field and near-field ventricular electrograms (EGMs) from stored implantable cardioverter-defibrillator (ICD) events of VT may be used to distinguish AS from IL VT in NICM. We analyzed 48 patients with NICM with either a primarily AS (54%) or IL (56%) VT source undergoing catheter ablation between 2003 and 2018. Only patients with retrievable ICD-EGMs of spontaneous VT events which could be matched with VTs induced during the ablation procedure were included. A total of 56 VT events (52% AS origin and 48% IL origin) were analyzed, yielding a mean far-field to near-field interval of 31 ± 13 milliseconds for AS VTs and 47 ± 19 milliseconds for IL VTs (P = .001). At receiver operating characteristic analysis (AUC = 0.734), a far-field to near-field interval of ≥ 60 milliseconds ruled out AS VTs in 29 (100%) cases and diagnosed IL VTs with a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 63%. An interval of ≤ 20 milliseconds ruled out IL VTs in 25 (93%) cases and diagnosed AS VTs with a PPV of 83% and NPV of 57%. Significant overlap between the two groups was observed among far-field to near-field intervals in between 20 milliseconds and 60 milliseconds. The relative timing of far-field and near-field EGMs from stored clinical ICD events of VT can be helpful to differentiate AS vs IL origin of VT in NICM.


Situational analysis for informing the global strengthening of the occupational therapy workforce.
Occupational Therapists are needed for meeting the health, rehabilitation, and occupational needs of the population worldwide, but there is no strategy for strengthening the occupational therapy workforce against a backdrop of an insufficient and inequitable supply worldwide. To perform a situational assessment of occupational therapy workforce development and research toward informing a global human resources strategy for the occupational therapy workforce strengthening. A multi-methods design incorporating Strengths, Weaknesses, Opportunities and Threats (SWOT) analysis based on scoping review findings, workforce development frameworks, and expert feedback. Strengths included identified workforce research trends, gaps, and findings. Weaknesses included a shortage of workforce research, lack of uniform and readily available workforce datasets, absence of workforce research programs, over-reliance on descriptive and non-experimental research, lack of research on workforce topics (e.g., diversity), and lack of labor market or economic analyses. Opportunities are the availability of guidance and tools for strengthening the health and rehabilitation workforce worldwide, and increased membership from low- and middle-income countries (LMICs) in the World Federation of Occupational Therapists. Threats include the suboptimal funding of occupational therapy workforce research, the lack of occupational therapists data on international datasets and studies, suboptimal educational capacity in LMICs, lack of professional regulation and uniform workforce data collection in many contexts, and a perceived lower priority of this health workforce focused on health and wellbeing rather than medical outcomes. This SWOT analysis identifies strengths and opportunities to be seized and weaknesses and threats to be addressed by development of a strategy for the global strengthening of the occupational therapy workforce.


Extended antibiotic therapy is associated with a lower rate of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy in intermediate- and high-risk patients: A single-institution analysis.
Clinically relevant postoperative pancreatic fistula remains a common complication after pancreatoduodenectomy. The fistula risk score is a validated tool to predict the risk of clinically relevant postoperative pancreatic fistula. To mitigate complications, we have implemented an extended antibiotic pathway for patients at increased risk of clinically relevant postoperative pancreatic fistula (fistula risk score ≥3). We report outcomes after pancreatoduodenectomy in patients at increased risk for clinically relevant postoperative pancreatic fistula who received extended antibiotic therapy compared to those who received standard perioperative antibiotics (single dose before incision). Single-institution analysis of 87 patients who underwent elective pancreatoduodenectomy (2018-2022) with soft gland texture and fistula risk score ≥3 and were treated with (n = 34) or without (n = 53) 10 days of broad-spectrum antibiotics (piperacillin/tazobactam converted to amoxicillin/clavulanic acid at discharge) after surgery. Associations between extended antibiotics and postoperative outcomes were analyzed. Baseline clinicodemographic factors were similar between cohorts. Patients who received extended antibiotics had shorter index days (6 vs 8 days, P = .004) and 90-day composite length of stay (8.5 vs 12 days, P = .018). Patients who received extended antibiotics had lower rates of clinically relevant postoperative pancreatic fistula (11.8% vs 37.7%; odds ratio = 0.17, 95% confidence interval: 0.04-0.68), wound infections (8.8% vs 30.2%; odds ratio = 0.08, 95% confidence interval: 0.01-0.50), organ space infections (14.7% vs 43.4%; odds ratio = 0.15, 95% confidence interval: 0.04-0.52), and image-guided drain placement (8.8% vs 34.0%; odds ratio = 0.15, 95% confidence interval: 0.04-0.62). There were no Clostridium difficile infections in the extended antibiotic group. Extended antibiotic therapy is associated with a lower rate of clinically relevant postoperative pancreatic fistula and associated complications after pancreatoduodenectomy in patients with a fistula risk score ≥3. These results form the basis of a randomized controlled trial (NCT05753735).


Women's experience of acute and chronic pain following breast cancer surgery.
To gain knowledge of how women experience pain and pain treatment after breast cancer surgery and to identify areas of pain management that they believe could be improved. According to the literature, 20-60% of patients develop chronic pain after breast cancer surgery and treatment. Because of the short length of hospitalisation in Norway, breast cancer patients are left responsible for most of their own pain management. An explorative and qualitative design was chosen. In-depth interviews were conducted with eight women who experienced chronic pain rated at 3-5 on a 11-point numerical rating scale one year or more after breast cancer surgery. This study is part of a larger, quantitative study assessing pain after surgery. The interviews were taped, transcribed and analysed according to qualitative content analysis. The interviewees had expected pain in the acute postoperative period, but had not expected that pain would persist. None of the women recalled having received information about pain. They took few analgesics and were generally sceptical about medication, mostly because of earlier reactions to drugs. They received no explanations for and little help with chronic pain. Most of them were active and worked outside the home. After short hospital stays, adequate information and follow-up after discharge may optimise pain management regimens. Those who develop chronic pain need more information and help to manage their pain. Finding the appropriate time for information about postoperative pain management is necessary to optimise a good analgesic regimen. Multimodal and aggressive treatment of acute pain should be emphasised.


Risk Factors and Clinical Outcomes of 54 Cases of Rectal Neuroendocrine Tumors with Incomplete Resection: A Retrospective Single-Center Study.
The present study aimed to analyze the risk factors and clinical outcomes of the incomplete endoscopic resection of rectal neuroendocrine tumors (rNETs). This study retrospectively analyzed the cases of 428 patients with rNETs who had undergone endoscopic treatment in the Department of Gastroenterology at the PLA General Hospital, China, between January 2010 and September 2019. Of the 428 patients with rNETs, 266 were men (62.1%) and 162 were women (37.9%). Of these, 54 had been pathologically diagnosed with positive incisal margins without lymphatic vessel invasion, and the incomplete resection (R1) rate was 12.6%. Among the R1 patients, 28 had received endoscopic submucosal dissection, 22 had received endoscopic mucosal resection, two had received snare resection, and two had undergone removal with forceps. In addition, there were 31 cases of grade G1 R1 resection (11.2%; 31/277), 13 cases of grade G2 R1 resection (23.2%; 13/56), and 10 cases whose grading was not described. The univariate analysis showed the pathological grade was statistically correlated with R1 resection (P < 0.05), and the grade G2 R1 resection rate was higher than that of grade G1. The multivariate logistic regression analysis showed that grade G2 was an independent risk factor leading to R1 resection (P = 0.02). All patients with R1 resection were followed up for 10-110 months, with an average of 38 months. No salvage treatment was performed. The endoscopic monitoring showed there were no recurrences during the follow-up period. Endoscopic resection is a good option for rNETs, with a high complete resection rate and good prognosis, with rare recurrence even if endoscopic resection is not complete.


Destruxin B inhibits hepatocellular carcinoma cell growth through modulation of the Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition.
The aberrant activation of Wnt/β-catenin signaling plays an important role in the carcinogenesis and progression of hepatocellular carcinoma (HCC). Therefore, the Wnt/β-catenin signaling molecules are attractive candidates for the development of targeted therapies for this disease. The present study showed that destruxin B (DB) inhibits the proliferation and induces the apoptosis of HCC cells by decreasing the protein expression of anti-apoptotic Bcl-2 and Bcl-xL and increasing the expression of the proapoptotic protein Bax. More importantly, DB also attenuates Wnt-signaling in HCC cells by downregulating β-catenin, Tcf4, and β-catenin/Tcf4 transcriptional activity, which results in the decreased expression of β-catenin target genes, such as cyclin D1, c-myc, and survivin. Furthermore, DB affects the migratory and invasive abilities of Sk-Hep1 cells through the suppression of markers of the epithelial-mesenchymal transition (EMT). A synergistic anti-proliferative and migratory effect was achieved using the combination of DB and sorafenib in Sk-Hep1 cells. In conclusion, DB acts as a novel Wnt/β-catenin inhibitor and reduces the aggressiveness and invasive potential of HCC by altering the cells' EMT status and mobility. DB in combination with sorafenib may be considered for future clinical use for the management of metastatic HCC.


DNA Barcoding and Pharmacovigilance of Herbal Medicines.
Pharmacovigilance of herbal medicines relies on the product label information regarding the ingredients and the adherence to good manufacturing practices along the commercialisation chain. Several studies have shown that substitution of plant species occurs in herbal medicines, and this in turn poses a challenge to herbal pharmacovigilance as adverse reactions might be due to adulterated or added ingredients. Authentication of constituents in herbal medicines using analytical chemistry methods can help detect contaminants and toxins, but are often limited or incapable of detecting the source of the contamination. Recent developments in molecular plant identification using DNA sequence data enable accurate identification of plant species from herbal medicines using defined DNA markers. Identification of multiple constituent species from compound herbal medicines using amplicon metabarcoding enables verification of labelled ingredients and detection of substituted, adulterated and added species. DNA barcoding is proving to be a powerful method to assess species composition in herbal medicines and has the potential to be used as a standard method in herbal pharmacovigilance research of adverse reactions to specific products.


Assessment of the iridocorneal angle pigmentation and structures after the implantation of EVO+ Visian Implantable Collamer Lens.
To evaluate the effect of EVO+ Visian Implantable Collamer Lens (ICL) implantation on the iridocorneal angle pigmentation and structures. Myopic refractive surgery candidates who underwent posterior chamber EVO+ ICL implantation were evaluated preoperatively and 3 and 6 months postoperatively. High-resolution images of the iridocorneal angle (nasal, superior, temporal and inferior quadrants) were acquired during gonioscopy. A masked observer, blinded to study visits and patients' information, evaluated the angle width, apparent iris root insertion, iris configuration, and trabecular meshwork pigmentation according to the Spaeth scale in two different occasions. The intra-rater reliability was estimated using the weighted Gwet's Agreement Coefficient (AC2). Differences between visits were analyzed using the Cochran Q test or the Friedman test. Twenty-one patients (13 females and 8 males) aging 31.3 ± 6.3 years old were recruited. The intra-rater reliability of gonioscopy assessment was excellent for every parameter assessed (AC2 ≥ 0.97). No significant differences were found among the study visits for any quadrant in the angle width (p ≥ 0.74), apparent iris root insertion (p ≥ 0.22), iris configuration (p ≥ 0.21) and trabecular meshwork pigmentation (p ≥ 0.24). Mean pigmentation of trabecular meshwork for the four quadrants did not vary either among visits (p = 0.25). The EVO+ ICL implantation after uneventful procedures appears not to clinically affect the iridocorneal angle pigmentation and/or structures during a short-medium follow-up using gonioscopy assessment. The intra-rater reliability of glaucoma specialists assessing iridocorneal angle structures using gonioscopy images is very high.


Characteristics of pancreatic diabetes in patients with autoimmune pancreatitis.
Although patients with autoimmune pancreatitis (AIP) tend to have concurrent diverse disorders, very few studies have focused on diabetes mellitus (DM) coexisting with AIP. In total 102 AIP patients with DM were divided into three groups. Those with DM before the onset of AIP were labeled group A (n=35), those who developed DM and AIP simultaneously were labeled group B (n=58) and those who developed DM after steroid therapy for AIP were labeled group C (n=9). The characteristics of DM among the three groups were evaluated. No significant differences were noted in the age of DM onset among the three groups. However, the mean duration of DM was significantly longer in group A (8.7 years) than in groups B and C. AIP developed 6.8 years after DM onset in group A, whereas it developed 1.8 years after steroid therapy in group C. Group A had the highest rate (25.7%) of family members with a history of AIP. Levels of serum albumin, total cholesterol and triglyceride were significantly lower in group A. No correlations were found between glycated hemoglobin and benzoyl-tyrosyl para-aminobenzoic acid. Hypoglycemia was observed in 20% of patients under insulin therapy. Most of them were habitual drinkers and received no pancreatic enzymes. Group A showed a high prevalence of retinopathy, nephropathy and macrovascular disorders than group B. Aspects of AIP-associated pancreatic diabetes were clarified. AIP-associated DM must be controlled by a full assessment of the pancreatic endocrine and exocrine function.


The Single Nucleotide Polymorphisms (rs1292037 and rs13137) in miR-21 Were Associated with T2DM in a Chinese Population.
Insulin receptor (INSR), insulin receptor substrate (IRS) and glucose transporter 4 (GLUT4) play important roles in the insulin resistance pathway. The microRNA (miRNA or miR) involved in INSR, IRS or GLUT4 could be associated with the development of type 2 diabetes (T2DM). The aim of this study was to investigate the association of T2DM with 12 single nucleotide polymorphisms (SNPs) in 7 miRNAs (miR-195, miR-126, miR-144, miR-155, miR-21, miR-93 and miR-222) involved in the insulin resistance pathway. A total of 1593 subjects with T2DM and 1656 nondiabetic subjects were genotyped. Then, the associations of these SNPs with the development of T2DM and individual metabolic traits were evaluated, such as fasting plasma glucose (FPG) and glycosylated haemoglobin (HbA1C). Our data showed that the C allele of rs1292037 in miR-21 could increase the risk of developing T2DM (P = 0.002, OR = 1.17; 95% CI: 1.06-1.29). In addition, the T allele of rs13137 in miR-21 could be a risk factor for T2DM (P = 0.003, OR = 1.16; 95% CI: 1.05-1.28). According to inheritance mode analysis, compared with the T/T-T/C genotype, the C/C genotype of rs1292037 showed a risk effect in T2DM in the recessive mode (P = 0.001, OR = 1.35; 95% CI: 1.13-1.63). For rs13137, compared with the A/A-A/T genotype, the T/T genotype also showed a risk effect in T2DM in the recessive mode (P = 0.001, OR = 1.35; 95% CI: 1.13-1.62). Moreover, in the nondiabetic group, compared with the rs78312845 A/G (FPG = 5.177±0.488mmol/L; HbA1C = 5.147±0.293%) and A/A genotypes (FPG = 5.155±0.486mmol/L; HbA1C = 5.136±0.299%), the G/G genotype (FPG = 4.887±0.482mmol/L; HbA1C = 4.960±0.397%) was associated with lower FPG (P = 0.012 and 0.019) and HbA1C (P = 0.008 and 0.011). Our results revealed that rs1292037 and rs13137 in miR-21 were associated with T2DM susceptibility in a Han Chinese population. Moreover, the rs78312845 in miR-195 contributed to the level of FPG and HbA1C in nondiabetic group in the Han Chinese population.


Flexible interferometric null testing for concave free-form surfaces using a hybrid refractive and diffractive variable null.
Free-form surfaces have been applied in a wide range of modern optical systems. As a supporting technique for fabricating free-form surfaces, the interferometric null method for testing the surface figure error has very limited flexibility. In this Letter, we report a flexible interferometric null test method which can test free-form surfaces with a very broad departure varying range. In the presented flexible null method, a hybrid refractive and diffractive variable null (HRDVN) is utilized as the flexible null. The HRDVN has superb aberration types adaptability, amplitude adaptability, and moderate phase generating accuracy. A flexible interferometric null testing setup was established using the HRDVN. Its superb adaptive capacity and moderate test accuracy were successfully demonstrated by measuring a free-form surface with rotationally symmetric departure of 173.486λ (λ=632.8 nm) and non-rotationally symmetric departure of 23.786λ.


[Genetic diagnostics of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease)].
Introduction: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant multisystemic vascular disease with a worldwide prevalence of 1 : 5000 - 1 : 10 000. Diagnosis is based on clinical Curacao criteria. Approximately 85% of HHT cases have heterozygous family-specific mutations in the ENG or ACVRL1 genes. Aim: We investigated 23 Hungarian HHT families, established the genetic diagnosis, executed family-screening and confirmed founder effects. Method: Probands were identified by the stratified population screening of the primary attendance area of our institution and from individuals contacting our study group voluntarily. Diagnosis is based on the otorhinolaryngological physical examination completed with characteristic telangiectasis sites, a visceral arteriovenous malformation screening and the sequence analysis of ENG and ACVRL1 genes. The family screening consists of physical examination and genetic screening for the family-specific mutation, followed by the arteriovenous malformation screening in patients with definite/suspected HHT and/or in individuals with the mutation. Results: Sixty-three individuals with family-specific mutations were identified in 22 families, 48 of them with definite and 12 with suspected HHT. Seven ENG and ACVRL1 mutations were detected, respectively; most of these are pathogenic. Three founder mutations were observed. One proband with definite HHT had wild-type alleles in all tested HHT-specific loci. Conclusions: The significance of genetic testing is confirming or excluding HHT in young asymptomatic individuals in families with pathogenic mutations. As ENG and ACVRL1 mutations result in overlapping fenotypes, the genetic testing lacks any prognostic value. The identification of founder effects might simplify the genetic diagnosis of new HHT patients from a given region. Orv Hetil. 2019; 160(18): 710-719.


Interleukin 22 serum levels are associated with radiographic progression in rheumatoid arthritis.
To study the role of interleukin 22 (IL-22) in rheumatoid arthritis (RA). IL-22 serum levels were measured in patients with early, treatment-naive RA (n=49) and in 45 age- and sex-matched healthy individuals as controls. Patients were assessed clinically and radiographically at baseline and followed up for 2 years. Correlations of IL-22 serum levels were sought with parameters of disease activity, serological markers, demographic factors and the incidence of erosions. IL-22 production by peripheral blood T cells was investigated by intracellular flow cytometry. 24 of 49 patients with RA demonstrated elevated IL-22 levels compared with the range of healthy controls. At baseline, a high percentage of these patients (8/24, 33%) demonstrated bone erosions, whereas only one patient (4%) from the group with normal IL-22 had erosions. During the 2 years of follow-up, six additional patients with increased IL-22 at baseline developed erosions. In contrast, none of the patients in whom IL-22 levels were normal developed erosions despite similar treatment regimens. Multivariate regression analysis accounting for other parameters predictive for erosions, such as the presence of rheumatoid factor or anti-cyclic citrullinated peptide antibodies and disease activity, showed that elevated IL-22 baseline levels were independently and significantly associated with erosive RA. Cellular analysis demonstrated enhanced expression of IL-22 from CD4 T cells in RA. IL-22 is elevated in the serum of half of the patients with RA. Elevated serum IL-22 allows discrimination between patients with different radiographic progression and indicates a possible involvement of IL-22 in the pathophysiology of RA.


A New Type of Satellite Associated with Cassava Mosaic Begomoviruses.
Cassava mosaic disease (CMD), which is caused by single-stranded DNA begomoviruses, severely limits cassava production across Africa. A previous study showed that CMD symptom severity and viral DNA accumulation increase in cassava in the presence of a DNA sequence designated SEGS-2 (sequence enhancing geminivirus symptoms). We report here that when SEGS-2 is coinoculated with African cassava mosaic virus (ACMV) onto Arabidopsis thaliana, viral symptoms increase. Transgenic Arabidopsis with an integrated copy of SEGS-2 inoculated with ACMV also display increased symptom severity and viral DNA levels. Moreover, SEGS-2 enables Cabbage leaf curl virus (CaLCuV) to infect a geminivirus-resistant Arabidopsis thaliana accession. Although SEGS-2 is related to cassava genomic sequences, an earlier study showed that it occurs as episomes and is packaged into virions in CMD-infected cassava and viruliferous whiteflies. We identified SEGS-2 episomes in SEGS-2 transgenic Arabidopsis. The episomes occur as both double-stranded and single-stranded DNA, with the single-stranded form packaged into virions. In addition, SEGS-2 episomes replicate in tobacco protoplasts in the presence, but not the absence, of ACMV DNA-A. SEGS-2 episomes contain a SEGS-2 derived promoter and an open reading frame with the potential to encode a 75-amino acid protein. An ATG mutation at the beginning of the SEGS-2 coding region does not enhance ACMV infection in A. thaliana. Together, the results established that SEGS-2 is a new type of begomovirus satellite that enhances viral disease through the action of an SEGS-2-encoded protein that may also be encoded by the cassava genome. IMPORTANCE Cassava is an important root crop in the developing world and a food and income crop for more than 300 million African farmers. Cassava is rising in global importance and trade as the demands for biofuels and commercial starch increase. More than half of the world's cassava is produced in Africa, where it is primarily grown by smallholder farmers, many of whom are from the poorest villages. Although cassava can grow under high temperature, drought, and poor soil conditions, its production is severely limited by viral diseases. Cassava mosaic disease (CMD) is one of the most important viral diseases of cassava and can cause up to 100% yield losses. We provide evidence that SEGS-2, which was originally isolated from cassava crops displaying severe and atypical CMD symptoms in Tanzanian fields, is a novel begomovirus satellite that can compromise the development of durable CMD resistance.


[Studies and safety evaluation of aflatoxins in herbal plants].
Herbs and herbal products are commonly used in food and pharmaceutical industries. The aim of this study was to test herbal plants for contamination with aflatoxins (AF), genotoxic, cancerogenic and hepatotoxic compounds which can cause immunotoxic and allergic effects as well as growth disorders. Aflatoxins were determined by high performance liquid chromatography (HPLC) with post column derivatization involving bromination with pyridinium hydrobromide perbromide (PBPB). Extracts was cleaned-up by immunoaffinity columns (IAC). The contents of aflatoxins B, B, G, and G, in more than 500 herbal plants samples mainly from Eastern Poland were investigated. Samples were supplied by manufacturers (herbal facilities) in 2006-2010 years. In all the evaluated samples the levels of aflatoxins above the detection limits of methods applied were not observed: for AF B1--0.2 microg/kg; AF B2--0.03 microg/kg; AF G1--0.3 microg/kg; AF G2--0.03 microg/kg (PN-EN 14123) and for AF B1--0.15 microg/kg (Ph. Eur.6, 2008:2.8.18). All the herbal plants tested for contamination with aflatoxins should be considered safe, which indicates that manufacturers used good manufacturing practices during drying and storage of raw materials.


Accurate surgical navigation with real-time tumor tracking in cancer surgery.
In the past decades, image-guided surgery has evolved rapidly. In procedures with a relatively fixed target area, like neurosurgery and orthopedics, this has led to improved patient outcomes. In cancer surgery, intraoperative guidance could be of great benefit to secure radical resection margins since residual disease is associated with local recurrence and poor survival. However, most tumor lesions are mobile with a constantly changing position. Here, we present an innovative technique for real-time tumor tracking in cancer surgery. In this study, we evaluated the feasibility of real-time tumor tracking during rectal cancer surgery. The application of real-time tumor tracking using an intraoperative navigation system is feasible and safe with a high median target registration accuracy of 3 mm. This technique allows oncological surgeons to obtain real-time accurate information on tumor location, as well as critical anatomical information. This study demonstrates that real-time tumor tracking is feasible and could potentially decrease positive resection margins and improve patient outcome.


Value of neck dissection in patients with cancer of the parotid gland and a clinical NO neck.
Cervical lymph node metastases in patients with parotid gland carcinoma are not rare. Regional metastases have a significant influence on the prognosis of these patients. In spite of the clinical relevance of lymphogenous metastases, the indications for elective treatment of the neck are not well defined. In the present review the controversies and therapeutical strategies of ipsilateral neck lymph nodes and their extension in patients with potential occult lymph node metastases are discussed. On the basis of the published data, in consideration of the direction of lymphogenous metastatic spread of parotid gland carcinomas, an elective neck dissection is recommended in carcinomas with high percentage of lymphatic spread also in the N0 neck. Consideration of additional parameters (> T2, lymphangiosis carcinomatosa) is appropriate to perform also a neck dissection in carcinomas with low risk for lymphogenous metastases. An elective neck dissection should include levels I, II, III and upper V.


Alteration of the actin-based cytoskeleton by rabies virus.
We investigated the effect of rabies virus infection on the actin cytoskeleton using various techniques. Confocal microscopic examination of rabies virus-infected neuroblastoma cells at late stages of infection revealed a dramatic decrease in F-actin staining. The results of a fluorimetric assay with pyrenylated actin indicated that purified rabies virus nucleocapsid has no direct action on the kinetics of actin polymerization and only a weak effect on the final extent of polymerization. Video-microscopy experiments with purified components showed that rabies virus nucleocapsid inhibits the actin-bundling effect induced by dephospho-synapsin I, a neuron-specific protein which is known to exert a control on the actin-based cytoskeleton. Thus, the observed decrease in F-actin staining in infected cells might be ascribed to an indirect action of rabies nucleocapsid on the effects of actin-binding proteins such as synapsin I.


Structure and immunogenicity of a peptide vaccine, including the complete HIV-1 gp41 2F5 epitope: implications for antibody recognition mechanism and immunogen design.
The membrane-proximal external region (MPER) of gp41 harbors the epitope recognized by the broadly neutralizing anti-HIV 2F5 antibody, a research focus in HIV-1 vaccine development. In this work, we analyze the structure and immunogenic properties of MPERp, a peptide vaccine that includes the following: (i) the complete sequence protected from proteolysis by the 2F5 paratope; (ii) downstream residues postulated to establish weak contacts with the CDR-H3 loop of the antibody, which are believed to be crucial for neutralization; and (iii) an aromatic rich anchor to the membrane interface. MPERp structures solved in dodecylphosphocholine micelles and 25% 1,1,1,3,3,3-hexafluoro-2-propanol (v/v) confirmed folding of the complete 2F5 epitope within continuous kinked helices. Infrared spectroscopy (IR) measurements demonstrated the retention of main helical conformations in immunogenic formulations based on alum, Freund's adjuvant, or two different types of liposomes. Binding to membrane-inserted MPERp, IR, molecular dynamics simulations, and characterization of the immune responses further suggested that packed helical bundles partially inserted into the lipid bilayer, rather than monomeric helices adsorbed to the membrane interface, could encompass effective MPER peptide vaccines. Together, our data constitute a proof-of-concept to support MPER-based peptides in combination with liposomes as stand-alone immunogens and suggest new approaches for structure-aided MPER vaccine development.


Large scale simulation of red blood cell aggregation in shear flows.
Aggregation of highly deformable red blood cells (RBCs) significantly affects the blood flow in the human circulatory system. To investigate the effect of deformation and aggregation of RBCs in blood flow, a mathematical model has been established by coupling the interaction between the fluid and the deformable solids. The model includes a three-dimensional finite volume method solver for incompressible viscous flows, the combined finite-discrete element method for computing the deformation of the RBCs, a JKR model-Johnson, Kendall and Roberts (1964-1971) (Johnson et al., 1971) to take account of the adhesion forces between different RBCs and an iterative direct-forcing immersed boundary method to couple the fluid-solid interactions. The flow of 49,512 RBCs at 45% concentration under the influence of aggregating forces was examined, improving the existing knowledge on simulating flow and structural characteristics of blood at a large scale: previous studies on the particular issue were restricted to simulating the flow of 13,000 aggregative ellipsoidal particles at a 10% concentration. The results are in excellent agreement with experimental studies. More specifically, both the experimental and the simulation results show uniform RBC distributions under high shear rates (60-100/s) whereas large aggregation structures were observed under a lower shear rate of 10/s. The statistical analysis of the simulation data also shows that the shear rate has significant influence on both the flow velocity profiles and the frequency distribution of the RBC orientation angles.


Controlling charge injection properties in polymer field-effect transistors by incorporation of solution processed molybdenum trioxide.
A simply and facilely synthesized MoO3 solution was developed to fabricate charge injection layers for improving the charge-injection properties in p-type organic field-effect transistors (OFETs). By dissolving MoO3 powder in ammonium (NH3) solvent under an air atmosphere, an intermediate ammonium molybdate ((NH4)2MoO4) precursor is made stable, transparent and spin-coated to form the MoO3 interfacial layers, the thickness and morphology of which can be well-controlled. When the MoO3 layer was applied to OFETs with a cost-effective molybdenum (Mo) electrode, the field-effect mobility (μFET) was significantly improved to 0.17 or 1.85 cm(2) V(-1)s(-1) for polymer semiconductors, regioregular poly(3-hexylthiophene) (P3HT) or 3,6-bis-(5bromo-thiophen-2-yl)-N,N'-bis(2-octyl-1-dodecyl)-1,4-dioxo-pyrrolo[3,4-c]pyrrole (DPPT-TT), respectively. Device analysis indicates that the MoO3-deposited Mo contact exhibits a contact resistance RC of 1.2 MΩ cm comparable to that in a device with the noble Au electrode. Kelvin-probe measurements show that the work function of the Mo electrode did not exhibit a dependence on the thickness of MoO3 film. Instead, ultraviolet photoemission spectroscopy results show that a doping effect is probably induced by casting the MoO3 layer on the P3HT semiconductor, which leads to the improved hole injection.


Effect of Q211 and K222 PRNP Polymorphic Variants in the Susceptibility of Goats to Oral Infection With Goat Bovine Spongiform Encephalopathy.
The prion protein-encoding gene (PRNP) is one of the major determinants for scrapie occurrence in sheep and goats. However, its effect on bovine spongiform encephalopathy (BSE) transmission to goats is not clear. Goats harboring wild-type, R/Q211 or Q/K222 PRNP genotypes were orally inoculated with a goat-BSE isolate to assess their relative susceptibility to BSE infection. Goats were killed at different time points during the incubation period and after the onset of clinical signs, and their brains as well as several peripheral tissues were analyzed for the accumulation of pathological prion protein (PrP(Sc)) and prion infectivity by mouse bioassay. R/Q211 goats displayed delayed clinical signs compared with wild-type goats. Deposits of PrP(Sc) were detected only in brain, whereas infectivity was present in peripheral tissues too. In contrast, none of the Q/K222 goats showed any evidence of clinical prion disease. No PrP(Sc) accumulation was observed in their brains or peripheral tissues, but very low infectivity was detected in some tissues very long after inoculation (44-45 months). These results demonstrate that transmission of goat BSE is genotype dependent, and they highlight the pivotal protective effect of the K222 PRNP variant in the oral susceptibility of goats to BSE.


A new locus for familial FSGS on chromosome 2p.
FSGS is a clinicopathologic entity characterized by nephrotic syndrome and progression to ESRD. Although the pathogenesis is unknown, the podocyte seems to play a central role in this disorder. Here, we present six kindreds with hereditary FSGS that did not associate with mutations in known causal genes, and we report a new locus for the disease on chromosome 2p15 in one kindred. We performed genome-wide linkage analysis and refined the linkage area with microsatellite markers and haplotype analysis to define the minimal candidate region. Genome-wide linkage analysis yielded a maximum two-point logarithm of odds (LOD) score of 3.6 for the six families on chromosome 2p. One family contributed the largest proportion of the additive score (LOD 2.02) at this locus. Multipoint parametric LOD score calculation in this family yielded a significant LOD score of 3.1 at markers D2S393 and D2S337, and fine mapping of this region with microsatellite markers defined a minimal candidate region of 0.9 Mb with observed recombinations at markers D2S2332 and RS1919481. We excluded the remaining five families from linkage to this region by haplotype analysis. These data support a new gene locus for familial FSGS on chromosome 2p15. Identification of the mutated gene at this locus may provide further insight into the disease mechanisms of FSGS.


Immune Regulation of Plasmodium Is Anopheles Species Specific and Infection Intensity Dependent.
Malaria parasite ookinetes must traverse the vector mosquito midgut epithelium to transform into sporozoite-producing oocysts. The Anopheles innate immune system is a key regulator of this process, thereby determining vector competence and disease transmission. The role of Anopheles innate immunity factors as agonists or antagonists of malaria parasite infection has been previously determined using specific single Anopheles-Plasmodium species combinations. Here we show that the two C-type lectins CTL4 and CTLMA2 exert differential agonistic and antagonistic regulation of parasite killing in African and South American Anopheles species. The C-type lectins regulate both parasite melanization and lysis through independent mechanisms, and their implication in parasite melanization is dependent on infection intensity rather than mosquito-parasite species combination. We show that the leucine-rich repeat protein LRIM1 acts as an antagonist on the development of Plasmodium ookinetes and as a regulator of oocyst size and sporozoite production in the South American mosquito Anopheles albimanus Our findings explain the rare observation of human Plasmodium falciparum melanization and define a key factor mediating the poor vector competence of Anopheles albimanus for Plasmodium berghei and Plasmodium falciparumIMPORTANCE Malaria, one of the world's deadliest diseases, is caused by Plasmodium parasites that are vectored to humans by the bite of Anopheles mosquitoes. The mosquito's innate immune system is actively engaged in suppressing Plasmodium infection. Studies on mosquito immunity revealed multiple factors that act as either facilitators or inhibitors of Plasmodium infection, but these findings were mostly based on single Anopheles-Plasmodium species combinations, not taking into account the diversity of mosquito and parasite species. We show that the functions of CTL4 and CTLMA2 have diverged in different vector species and can be both agonistic and antagonistic for Plasmodium infection. Their protection against parasite melanization in Anopheles gambiae is dependent on infection intensity, rather than the mosquito-parasite combination. Importantly, we describe for the first time how LRIM1 plays an essential role in Plasmodium infection of Anopheles albimanus, suggesting it is a key regulator of the poor vector competence of this species.


Multimodal genomic features predict outcome of immune checkpoint blockade in non-small-cell lung cancer.
Despite progress in immunotherapy, identifying patients that respond has remained a challenge. Through analysis of whole-exome and targeted sequence data from 5,449 tumors, we found a significant correlation between tumor mutation burden (TMB) and tumor purity, suggesting that low tumor purity tumors are likely to have inaccurate TMB estimates. We developed a new method to estimate a corrected TMB (cTMB) that was adjusted for tumor purity and more accurately predicted outcome to immune checkpoint blockade (ICB). To identify improved predictive markers together with cTMB, we performed whole-exome sequencing for 104 lung tumors treated with ICB. Through comprehensive analyses of sequence and structural alterations, we discovered a significant enrichment in activating mutations in receptor tyrosine kinase (RTK) genes in nonresponding tumors in three immunotherapy treated cohorts. An integrated multivariable model incorporating cTMB, RTK mutations, smoking-related mutational signature and human leukocyte antigen status provided an improved predictor of response to immunotherapy that was independently validated.


Kinetic model of hydrocortisone 1-en-dehydrogenation by Arthrobacter globiformis.
A kinetic model of the hydrocortisone-to-prednisolone transformation by Arthrobacter globiformis is constructed using the experimental data obtained in studies of this process. Besides adequately describing experimental data, the model allows one to determine the relation between hydrocortisone oxidation and the level of endogenous substrates in bacterial cells, and the relation between the saturating concentration of hydrocortisone in the enzymic system of bacteria and the content of endogenous substrates in their cells, as well as the regulation of the transmembrane potential and the activation by the uncouplers.


Distinct clinical profiles and post-transplant outcomes among kidney transplant recipients with lower education levels: uncovering patterns through machine learning clustering.
Educational attainment significantly influences post-transplant outcomes in kidney transplant patients. However, research on specific attributes of lower-educated subgroups remains underexplored. This study utilized unsupervised machine learning to segment kidney transplant recipients based on education, further analyzing the relationship between these segments and post-transplant results. Using the OPTN/UNOS 2017-2019 data, consensus clustering was applied to 20,474 kidney transplant recipients, all below a college/university educational threshold. The analysis concentrated on recipient, donor, and transplant features, aiming to discern pivotal attributes for each cluster and compare post-transplant results. Four distinct clusters emerged. Cluster 1 comprised younger, non-diabetic, first-time recipients from non-hypertensive younger donors. Cluster 2 predominantly included white patients receiving their first-time kidney transplant either preemptively or within three years, mainly from living donors. Cluster 3 included younger re-transplant recipients, marked by elevated PRA, fewer HLA mismatches. In contrast, Cluster 4 captured older, diabetic patients transplanted after prolonged dialysis duration, primarily from lower-grade donors. Interestingly, Cluster 2 showcased the most favorable post-transplant outcomes. Conversely, Clusters 1, 3, and 4 revealed heightened risks for graft failure and mortality in comparison. Through unsupervised machine learning, this study proficiently categorized kidney recipients with lesser education into four distinct clusters. Notably, the standout performance of Cluster 2 provides invaluable insights, underscoring the necessity for adept risk assessment and tailored transplant strategies, potentially elevating care standards for this patient cohort.


Placebo improvement in pharmacologic treatment of menopausal hot flashes: time course, duration, and predictors.
To characterize the time course, duration of improvement, and clinical predictors of placebo response in treatment of menopausal hot flashes. Data were pooled from two trials conducted in the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network, providing a combined placebo group (n = 247) and a combined active treatment group (n = 297). Participants recorded hot flash frequency in diaries twice daily during treatment (Weeks 0-8) and subsequent follow-up (Weeks 9-11). The primary outcome variable was clinically significant improvement, defined as a 50% or greater decrease in hot flash frequency from baseline and calculated for each week in the study. Subgroups were defined a priori using standard clinical definitions for significant improvement and partial improvement. Clinical and demographic characteristics of the participants were evaluated as predictors of improvement. Clinically significant improvement with placebo accrued each treatment week, with 33% significantly improved at Week 8. Of placebo responders who were improved at both Weeks 4 and 8, 77% remained clinically improved at Week 11 after treatment ended. Independent predictors of significant placebo improvement in the final multivariable model were African American race (odds ratio [OR] = 5.61, 95% confidence interval [CI] = 2.41-13.07, p < .001), current smokers (OR = 2.30, 95% CI = 1.05-5.06, p = .038), and hot flash severity in screening (OR = 1.45, 95% CI = 1.00-2.10, p = .047). Clinically significant improvement with placebo accrued throughout treatment with a time course similar to improvement with active drug. A meaningful number of participants in the placebo group sustained a clinically significant response after stopping placebo pills. The results suggest that nonspecific effects are important components of treatment and warrant further studies to optimize their contributions in clinical care.


External Memory Aid Preferences of Individuals with Mild Memory Impairments.
Individuals with mild memory impairments often rely on external memory aids (EMAs) to compensate for impaired cognitive abilities and to support independent completion of activities of daily living. These strategies are evidence based; however, professionals have limited knowledge regarding individual preferences and guidance on how to incorporate a person-centered approach into the EMA development phase. The purpose of the current study was to qualitatively investigate individuals' preferences and experiences as they relate to EMAs. Data analysis included (1) evaluation of a posttreatment questionnaire to explore individual strategy preferences following intervention and (2) evaluation of group intervention videos using thematic coding to investigate individuals' experiences with strategies during intervention. Results suggest that older adults with mild memory impairments have unique preferences and experiences, despite limited variability in demographic characteristics. Some themes that emerged included memory ability awareness and attitudes toward technology. Within a person-centered approach, skilled professionals must consider individuals' unique needs, preferences, and experiences when developing strategies throughout the continuum of care to promote sustained EMA use within everyday settings.


Differential responses of invariant V alpha 24J alpha Q T cells and MHC class II-restricted CD4+ T cells to dexamethasone.
NK T cells are a T cell subset in the human that express an invariant alpha-chain (V alpha 24invt T cells). Because of the well-described immunomodulation by glucocorticoids on activation-induced cell death (AICD), the effects of dexamethasone and anti-CD3 stimulation on V alpha 24invt T cell clones and CD4+ T cell clones were investigated. Dexamethasone significantly enhanced anti-CD3-mediated proliferation of V alpha 24invt T cells, whereas CD4+ T cells were inhibited. Addition of neutralizing IL-2 Ab partially abrogated dexamethasone-induced potentiation of V alpha 24invt T cell proliferation, indicating a role for autocrine IL-2 production in corticosteroid-mediated proliferative augmentation. Dexamethasone treatment of anti-CD3-stimulated V alpha 24invt T cells did not synergize with anti-Fas blockade in enhancing proliferation or preventing AICD. The V alpha 24invt T cell response to dexamethasone was dependent on the TCR signal strength. In the presence of dexamethasone, lower doses of anti-CD3 inhibited proliferation of V alpha 24invt T cells and CD4+ T cells; at higher doses of anti-CD3, which caused inhibition of CD4+ T cells, the V alpha 24invt T cell clones proliferated and were rescued from AICD. These results demonstrate significant differences in TCR signal strength required between V alpha 24invt T cells and CD4+ cells, and suggest important immunomodulatory consequences for endogenous and exogenous corticosteroids in immune responses.


Effects of protoscoleces excretory-secretory products of Echinococcus granulosus on hepatocyte growth, function, and glucose metabolism.
Cystic echinococcosis (CE) is one of the most widespread and harmful zoonotic parasitic diseases, which most commonly affects the liver. In this study, we characterized multiple changes in mouse hepatocytes following treatment with excretory-secretory products (ESPs) of Echinococcus granulosus protoscoleces (Eg-PSCs) by a factorial experiment. The cell counting kit-8 assay (CCK-8), the 5-ethynyl-2'-deoxyuridine (EdU) assay, and flow cytometry were used to detect the growth of hepatocytes. Inverted microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were used to observe the morphology and ultrastructure of hepatocytes. An automatic biochemical analyzer and an ELISA detection kit were used to determine six conventional hepatocyte enzymatic indices, the levels of five hepatocyte-synthesized substances, and the contents of glucose and lactate. Western blot analysis was conducted to analyze the protein expression of three apoptosis-related proteins, Bax, Bcl-2, cleaved caspase-3, and six glucose metabolism pathways rate-limiting enzymes in hepatocytes. The results showed that ESPs inhibited hepatocyte proliferation and promoted hepatocyte apoptosis. The cell membrane and microvilli of hepatocytes changed, and the nucleus, mitochondria and rough endoplasmic reticulum were damaged to varying degrees. The contents of iron, albumin (ALB), uric acid (UA) and urea were increased, and the activities of six enzymes in hepatocytes were increased except for the decrease of transferrin (TRF). The expression levels of all six key enzymes in the glucose metabolism pathway in hepatocytes were reduced. Our characterization provides a basis for further research on the pathogenesis, prevention and treatment of CE.


Comparison of blood pressure measurements between an automated oscillometric device and a Hawksley random-zero sphygmomanometer in the northern Sweden MONICA study.
The Hawksley random-zero sphygmomanometer (random-zero) has been used widely in epidemiological observation studies. This study compares blood pressure measurements using the random-zero with measurements using an automated oscillometric device and suggests a correction of the automated oscillometric measurements to enable comparisons of blood pressure levels over time. The northern Sweden MONICA population survey 2009 included 1729 participants, 853 men and 876 women, 25-74 years old. Blood pressure was measured using both random-zero and an automated oscillometric device in all participants. The Omron M7 digital blood pressure monitor was used for automated oscillometric measurements. A linear mixed model was used to derive a formula to adjust the automated oscillometric readings. Automated oscillometric measurements of systolic blood pressure were generally lower than random-zero measurements in women [oscillometric mean 122.1 mmHg (95% confidence interval: 121.0-123.2) versus random-zero mean 124.4 mmHg (123.5-125.5)], whereas automated oscillometric measurements of systolic blood pressure were generally higher than random-zero measurements in men [oscillometric 131.1 mmHg (130.0-132.2) versus random-zero 129.0 mmHg (127.9-130.1)]. For diastolic blood pressure, automated oscillometric measurements were higher in both women [oscillometric 79.9 mmHg (79.2-80.5) versus random-zero 76.7 mmHg (76.0-77.4)] and men [oscillometric 83.1 mmHg (82.4-83.8) vs. random-zero 81.2 mmHg (80.6-81.9)]. The difference also varied with age and order of measurement. Adjustment of the automated oscillometric measurements using mixed model regression coefficients produced estimates of blood pressure that were close to the random-zero measurements. Blood pressure measurements using an automated oscillometric device differ from those with random-zero, but the oscillometric measurements can be adjusted, on the basis of sex, age and measurement order, to be similar to the random-zero measurements.


Changes in Aqueous Concentrations of Various Cytokines after Intravitreal Bevacizumab Injection for Chronic Central Serous Chorioretinopathy.
This study aimed to investigate changes in cytokine levels after intravitreal bevacizumab injection in patients with chronic central serous chorioretinopathy (CSC). In a prospective interventional trial, 12 eyes from 12 patients with chronic CSC and six eyes from six patients who underwent cataract surgery were included as controls. Patients diagnosed as with CSC received a single intravitreal injection of bevacizumab (1.25 mg/0.05 mL). Aqueous humor samples were collected from the patients and controls. Best-corrected visual acuity and foveal thickness were evaluated, and aqueous samples were obtained before and 4 weeks after injection. The aqueous concentrations of interleukin (IL)-6, IL-8, interferon-induced protein (IP)-10, monocyte chemotactic protein (MCP)-1, platelet-derived growth factor (PDGF)-AA, and vascular endothelial growth factor (VEGF) were measured using a multiplex bead assay. After injection, the foveal thickness decreased significantly from 328.08 μm (range, 210-477 μm) to 283.91 μm (range, 168-356 μm; p = 0.048), but the best-corrected visual acuity was not significantly different (p = 0.066). The aqueous levels of IL-8 increased significantly from 3.3 pg/mL (range, 1.5-8.3 pg/mL) to 4.7 pg/mL (range, 2.2-11.6 pg/mL) at 4 weeks after the injection (p = 0.046). The aqueous levels of VEGF decreased significantly from 31.4 pg/mL (range, 17.0-53.3 pg/mL) to 15.2 pg/mL (range, 7.7-21.5 pg/mL; p < 0.01). No significant changes in levels of IL-6 (p = 0.455), IP-10 (p = 0.055), MCP-1 (p = 0.076), and PDGF-AA (p = 0.339) were noted 4 weeks after injection. In this study we found intravitreal bevacizumab injection decreased VEGF and increased IL-8 in the eyes of patients with chronic CSC. This study suggests the possibility that the pathogenesis of CSC may be related to abnormal circulation of the choroidal blood vessels through VEGF and IL-8 cytokine level changes.


Frequent and variable cytotoxic-T-lymphocyte escape-associated fitness costs in the human immunodeficiency virus type 1 subtype B Gag proteins.
Cytotoxic-T-lymphocyte (CTL) escape mutations undermine the durability of effective human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T cell responses. The rate of CTL escape from a given response is largely governed by the net of all escape-associated viral fitness costs and benefits. The observation that CTL escape mutations can carry an associated fitness cost in terms of reduced virus replication capacity (RC) suggests a fitness cost-benefit trade-off that could delay CTL escape and thereby prolong CD8 response effectiveness. However, our understanding of this potential fitness trade-off is limited by the small number of CTL escape mutations for which a fitness cost has been quantified. Here, we quantified the fitness cost of the 29 most common HIV-1B Gag CTL escape mutations using an in vitro RC assay. The majority (20/29) of mutations reduced RC by more than the benchmark M184V antiretroviral drug resistance mutation, with impacts ranging from 8% to 69%. Notably, the reduction in RC was significantly greater for CTL escape mutations associated with protective HLA class I alleles than for those associated with nonprotective alleles. To speed the future evaluation of CTL escape costs, we also developed an in silico approach for inferring the relative impact of a mutation on RC based on its computed impact on protein thermodynamic stability. These data illustrate that the magnitude of CTL escape-associated fitness costs, and thus the barrier to CTL escape, varies widely even in the conserved Gag proteins and suggest that differential escape costs may contribute to the relative efficacy of CD8 responses.


Experimental structure determination of the chemisorbed overlayers of chlorine and iodine on Au{111}.
We have performed an experimental structure determination of the ordered p(sqrt[3] x sqrt[3])R30 degrees structures of chlorine and iodine on Au{111} using low-energy electron diffraction (LEED). Despite great similarities in the structure of the underlying substrate, which shows only minor deviations from the bulk positions in both cases, chlorine and iodine are found to adsorb in different adsorption sites, fcc and hcp hollow sites, respectively. The experimental Au-Cl and Au-I bond lengths of 2.56 and 2.84 A are close to the sums of the covalent radii, supporting the view that the bond is essentially covalent in nature; however, they are significantly shorter than predicted theoretically.


The effects of family planning workers' contact on fertility preferences: evidence from Bangladesh.
Should family planning programs put more effort into persuading couples to want smaller families or into helping women achieve their reproductive goals? Indeed, can family planning programs affect fertility preferences? Longitudinal data from Bangladesh collected from 1982 to 1993 show that women's desired family sizes have declined dramatically. This study examines how the decline in desired family size is related to visits from family planning workers for three intervals: 1982-85, 1985-90, and 1990-93. By use of logistic-regression analysis, the number of rounds during which women received visits from family planning workers is found to have no statistically significant effect on the probability that women altered their preference from wanting more children at the beginning of an interval to wanting no more at the end of the interval.


Mechanisms of clinical resistance to fluoroquinolones in Staphylococcus aureus.
Mechanisms of Staphylococcus aureus resistance to fluoroquinolones were characterized. Subunit A and B proteins of DNA gyrase were partially purified from fluoroquinolone-susceptible strain SA113 and resistant isolate MS16405, which was 250- to 1,000-fold less susceptible to fluoroquinolones such as ciprofloxacin, norfloxacin, ofloxacin, temafloxacin, and sparfloxacin than SA113 was. The supercoiling activity of the gyrase from SA113 was inhibited by the fluoroquinolones, and the 50% inhibitory concentrations of the drugs correlated well with their MICs. In contrast, the gyrase from MS16405 was insensitive to inhibition of supercoiling by all of the quinolones tested, even at 800 micrograms/ml. Combinations of heterologous gyrase subunits showed that subunit A from MS16405 conferred fluoroquinolone resistance, suggesting that an alteration in gyrase subunit A is a cause of the fluoroquinolone resistance in MS16405. Uptake of hydrophilic fluoroquinolones such as ciprofloxacin and norfloxacin by MS16405 was significantly lower than that by SA113. Furthermore, this difference was abolished by the addition of an energy inhibitor, carbonyl cyanide m-chlorophenylhydrazone, suggesting that an alteration in an energy-dependent process, such as an active efflux of hydrophilic quinolones, may lead to decreased drug uptake and hence to increased resistance to fluoroquinolones in MS16405. These findings suggest that the fluoroquinolone resistance in MS16405 is due mainly to an alteration in subunit A of DNA gyrase and may also be associated with an alteration in the drug uptake process.


[Indebtedness and mortality: analysis at county and city levels in Germany].
Little is known about the influence of individual debts on health inequalities in Germany. Studies from English-language countries have shown that indebtedness is a great burden in every-day life that leads to mental stress and is related to negative health outcomes. Our paper, for the first time, analyses the role of indebtedness on mortality in Germany. Using ecological level data of Germany's 439 administrative districts, we assessed the role of unemployment, income, educational level, population density, regional prosperity, number of hospital beds and of the independent effect of indebtedness on mortality. The variance explained by indebtedness was determined by means of multiple linear regression models. Data were provided by the Federal Statistical Office of Germany and Schufa Holding AG. Indebtedness and unemployment are moderately correlated. Even so, a significant independent effect of indebtedness on mortality can be shown. Indebtedness contributes to the explanation of health inequalities and, together with other socioeconomic factors and the federal state, explains 59% of the variance in age-standardised district level mortality. Indebtedness explains 6% of variance. For the first time in Germany, this study shows that indebtedness not only influences population health as a result of low income or unemployment but also has an independent, albeit rather small, effect. Studies focussing on social inequity and health should further examine the role of indebtedness and also include an analysis on the individual level.


Molecular characterization of a novel astrovirus associated with disease in mink.
Pre-weaning diarrhoea is a well-known problem in mink farming in Europe, causing morbidity that varies between farms, regions and season. Different causalities for the disease have been proposed, but only most recently has a novel astrovirus been identified as an important risk factor. In this report, the molecular characterization, origin and evolution of this novel astrovirus of mink are discussed. The polyadenylated, positive-stranded RNA genome was sequenced and found to contain 6610 nt, organized into three ORFs and two short UTRs. A ribosomal frameshift sequence links the 5' two ORFs, containing sequence motifs for a serine protease (ORF1a) and an RNA-dependent RNA polymerase (ORF1b). The structural proteins are encoded by ORF2 and, presumably, are expressed as a polyprotein precursor to be cleaved into the mature capsid proteins. These results indicate that mink astrovirus (MiAstV) has all of the features typical of members of the Astroviridae. Phylogenetic analyses revealed that MiAstV is distantly related to established astroviruses, showing less than 67 % similarity at the nucleotide level with its closest relative, ovine astrovirus, and even lower identities at the predicted amino acid level. Nevertheless, sequence analysis of MiAstV isolates from geographically distinct Swedish and Danish farms showed much less diversity. This suggests either the spread in the mink population of a virus that has evolved a long time ago or the recent introduction of an ancient virus into a new host species.


Symmetry broken and rebroken during the ATP hydrolysis cycle of the mitochondrial Hsp90 TRAP1.
Hsp90 is a homodimeric ATP-dependent molecular chaperone that remodels its substrate 'client' proteins, facilitating their folding and activating them for biological function. Despite decades of research, the mechanism connecting ATP hydrolysis and chaperone function remains elusive. Particularly puzzling has been the apparent lack of cooperativity in hydrolysis of the ATP in each protomer. A crystal structure of the mitochondrial Hsp90, TRAP1, revealed that the catalytically active state is closed in a highly strained asymmetric conformation. This asymmetry, unobserved in other Hsp90 homologs, is due to buckling of one of the protomers and is most pronounced at the broadly conserved client-binding region. Here, we show that rather than being cooperative or independent, ATP hydrolysis on the two protomers is sequential and deterministic. Moreover, dimer asymmetry sets up differential hydrolysis rates for each protomer, such that the buckled conformation favors ATP hydrolysis. Remarkably, after the first hydrolysis, the dimer undergoes a flip in the asymmetry while remaining in a closed state for the second hydrolysis. From these results, we propose a model where direct coupling of ATP hydrolysis and conformational flipping rearranges client-binding sites, providing a paradigm of how energy from ATP hydrolysis can be used for client remodeling.


[Prognostic value of serum beta2-microglobulin in multiple myeloma].
We have analysed a series of 96 patients with multiple myeloma (MM) to the purpose to verify the prognostic meaning of the beta2-microglobulin (B2M) and the validity of the staging systems proposed by Bataille and Jacobson who use the B2M respectively associated to the serum C-reactive protein (CRP) and to the serum albumin. In our series of patients the serum level of B2M at the diagnosis was directly correlated with the myelomatous cellular mass. We have found besides an inverse correlation between B2M and survival. Also the serum level of CRP was inversely correlated with the survival, while a direct correlation was found between the serum albumin and the survival: ipoalbuminemia was confirmed as a predictive index of short survival. Staging our patients with MM according to the proposal of Bataille, we identified also in our series three prognostic groups with different median survival: respectively 72, 40 and 18 months. Applying finally the staging proposal of Jacobson to our series, four stages were individualized, with median survival respectively of 70, 52, 26 and 10 months. We confirm the prognostic value of the B2M in MM.


Chromosome cohesion - rings, knots, orcs and fellowship.
Sister-chromatid cohesion is essential for accurate chromosome segregation. A key discovery towards our understanding of sister-chromatid cohesion was made 10 years ago with the identification of cohesins. Since then, cohesins have been shown to be involved in cohesion in numerous organisms, from yeast to mammals. Studies of the composition, regulation and structure of the cohesin complex led to a model in which cohesin loading during S-phase establishes cohesion, and cohesin cleavage at the onset of anaphase allows sister-chromatid separation. However, recent studies have revealed activities that provide cohesion in the absence of cohesin. Here we review these advances and propose an integrative model in which chromatid cohesion is a result of the combined activities of multiple cohesion mechanisms.


Dyslexia and dysgraphia of primary progressive aphasia in Chinese: A systematic review.
Currently, little is known about Chinese-speaking primary progressive aphasia (PPA) patients compared to patients who speak Indo-European languages. We examined the demographics and clinical manifestations, particularly reading and writing characteristics, of Chinese patients with PPA over the last two decades to establish a comprehensive profile and improve diagnosis and care. We reviewed the demographic features, clinical manifestations, and radiological features of Chinese-speaking PPA patients from 56 articles published since 1994. We then summarized the specific reading and writing errors of Chinese-speaking patients. The average age of onset for Chinese-speaking patients was in their early 60's, and there were slightly more male patients than female patients. The core symptoms and images of Chinese-speaking patients were similar to those of patients who speak Indo-European languages. Reading and writing error patterns differed due to Chinese's distinct tone and orthography. The types of reading errors reported in Chinese-speaking patients with PPA included tonal errors, regularization errors, visually related errors, semantic errors, phonological errors, unrelated errors, and non-response. Among these errors, regularization errors were the most common in semantic variant PPA, and tonal errors were specific to Chinese. Writing errors mainly consisted of non-character errors (stroke, radical/component, visual, pictograph, dyskinetic errors, and spatial errors), phonologically plausible errors, orthographically similar errors, semantic errors, compound word errors, sequence errors, unrelated errors, and non-response. This paper provides the latest comprehensive demographic information and unique presentations on the reading and writing of Chinese-speaking patients with PPA. More detailed studies are needed to address the frequency of errors in reading and writing and their anatomical substrates.


Gestational carcinoma of the female breast.
Few neoplastic diseases can equal the amazing complexity and sheer perversity of carcinoma of the breast. No doubt as many decades of research lie ahead in its study as already have passed. Clinicians have long appreciated the special relationship of the disease to gestation. Diagnosis and treatment of breast cancer during pregnancy represent only a small part of this fascinating relationship. Although indispensable as research tools, animal models pertain to the human disease only in limited, ill-defined ways. The etiology of human breast cancer remains unclear; chemical, viral, hormonal, genetic, and immunologic theories have all been put forward as possibilities. Although gestation clearly alters both the initiation and growth of mammary tumors, its exact role in the various theoretical considerations remains a mystery. The obstetrician-gynecologist holds an important front-line position in the war against breast cancer, as does any provider of primary care to women, and, indeed, as do women themselves. Rather than decrease vigilance during pregnancy, the physician should pursue with extra vigor any breast mass discovered in the gravid patient, when the clinical examination is even less reliable than usual. The finding of a breast mass usually necessitates biopsy. Except for the inclusion of specific pregnancy-related problems, such as galactocele, the diagnostic spectrum of breast masses removed during pregnancy does not differ from that in nonpregnant women. The discovery of a highly suspicious breast mass, or the confirmed biopsy diagnosis of malignancy, in a pregnant patient should indicate the need for referral to a surgical oncologist versed in this unusual problem. The best approach to gestational breast cancer continues to be the team approach, with consultation from specialists in obstetrics, surgical oncology, anesthesiology, nuclear medicine, radiology, radiation oncology, pathology, and medical oncology. The age and general condition of the patient, the extent of the tumor, the stage of gestation, and the informed opinions of the patient and her spouse help to determine the therapeutic strategy. Careful staging not only guides present therapy but also the therapy of future victims through continued investigation. Most surgeons favor operation without delay if cure seems within reach. Mastectomy, with or without cesarean section, can be accomplished without detriment in the hands of a knowledgeable surgeon-anesthesiologist team. By following certain guidelines, the search for metastasis can be conducted safely and appropriately. The clinical situation occasionally may require the initiation of adjuvant radiotherapy or chemotherapy during pregnancy, by experienced consultants. Ongoing studies of tissue hormone receptors and cell kinetics will continue to give insight into the effects of gestational hormones on breast cancer and can aid in the selection of treatment options for the individual patient...


FlbD, a Myb transcription factor of Aspergillus nidulans, is uniquely involved in both asexual and sexual differentiation.
In the fungus Aspergillus nidulans, inactivation of the flbA to -E, fluG, fluF, and tmpA genes results in similar phenotypes, characterized by a delay in conidiophore and asexual spore production. flbB to -D encode transcription factors needed for proper expression of the brlA gene, which is essential for asexual development. However, recent evidence indicates that FlbB and FlbE also have nontranscriptional functions. Here we show that fluF1 is an allele of flbD which results in an R47P substitution. Amino acids C46 and R47 are highly conserved in FlbD and many other Myb proteins, and C46 has been proposed to mediate redox regulation. Comparison of ΔflbD and flbD(R47P) mutants uncovered a new and specific role for flbD during sexual development. While flbD(R47P) mutants retain partial function during conidiation, both ΔflbD and flbD(R47P) mutants are unable to develop the peridium, a specialized external tissue that differentiates during fruiting body formation and ends up surrounding the sexual spores. This function, unique among other fluffy genes, does not affect the viability of the naked ascospores produced by mutant strains. Notably, ascospore development in these mutants is still dependent on the NADPH oxidase NoxA. We generated R47K, C46D, C46S, and C46A mutant alleles and evaluated their effects on asexual and sexual development. Conidiation defects were most severe in ΔflbD mutants and stronger in R47P, C46D, and C46S strains than in R47K strains. In contrast, mutants carrying the flbD(C46A) allele exhibited conidiation defects in liquid culture only under nitrogen starvation conditions. The R47K, R47P, C46D, and C46S mutants failed to develop any peridial tissue, while the flbD(C46A) strain showed normal peridium development and increased cleistothecium formation. Our results show that FlbD regulates both asexual and sexual differentiation, suggesting that both processes require FlbD DNA binding activity and that FlbD is involved in the response to nitrogen starvation.


From concepts, theory, and evidence of heterogeneity of treatment effects to methodological approaches: a primer.
Implicit in the growing interest in patient-centered outcomes research is a growing need for better evidence regarding how responses to a given intervention or treatment may vary across patients, referred to as heterogeneity of treatment effect (HTE). A variety of methods are available for exploring HTE, each associated with unique strengths and limitations. This paper reviews a selected set of methodological approaches to understanding HTE, focusing largely but not exclusively on their uses with randomized trial data. It is oriented for the "intermediate" outcomes researcher, who may already be familiar with some methods, but would value a systematic overview of both more and less familiar methods with attention to when and why they may be used. Drawing from the biomedical, statistical, epidemiological and econometrics literature, we describe the steps involved in choosing an HTE approach, focusing on whether the intent of the analysis is for exploratory, initial testing, or confirmatory testing purposes. We also map HTE methodological approaches to data considerations as well as the strengths and limitations of each approach. Methods reviewed include formal subgroup analysis, meta-analysis and meta-regression, various types of predictive risk modeling including classification and regression tree analysis, series of n-of-1 trials, latent growth and growth mixture models, quantile regression, and selected non-parametric methods. In addition to an overview of each HTE method, examples and references are provided for further reading.By guiding the selection of the methods and analysis, this review is meant to better enable outcomes researchers to understand and explore aspects of HTE in the context of patient-centered outcomes research.


Biosecurity risks associated with current identification practices of producers trading live pigs at livestock sales.
Approximately 5% of pigs produced in Australia is believed to be traded at livestock sales. Interviews and focus group discussions were conducted with producers (106 and 30 producers, respectively), who traded pigs at livestock sales. The purpose of the study was to gather information on how producers identified their pigs in order to evaluate how these practices may impact the ability to trace pig movements in the event of an emergency animal disease outbreak or food safety hazard. Results were analyzed according to herd size (0 to 150 sows, 150+ sows) and location (peri-urban, regional) as prior studies suggested a higher biosecurity risk among smaller farms and due to perceptions that peri-urban farms pose additional risk. Most producers (91.5%) had less than 150 sows and a high proportion (70.8%) resided in regional areas compared with only 29.2% residing in peri-urban areas. A higher proportion of large-scale producers identified their pigs than small-scale producers. A third of small-scale producers reported not identifying breeding stock and most did not identify progeny. The most common forms of on-farm identification used were ear tags for breeding stock and ear notches for progeny. Producers identified breeding stock to assist with mating management and genetic improvement. Ear notches were used to determine the litter of origin of progeny. All large-scale producers owned a registered swine brand and used the official body tattoo for post-farm-gate identification. However, approximately 15% of small-scale producers did not own a registered swine brand, and an additional 8% did not identify their pigs post-farm-gate. Producers were satisfied with tattoos as a methodology for post-farm-gate identification of pigs and considered other methodologies cost-prohibitive. However, variations in the maintenance of the branding equipment, the type of ink used and the time of tattoo application in relation to the animal sale were highlighted during focus group discussions. These results suggest that there is a need for education and extension activities, especially among small-scale pig producers, regarding the benefits of identifying animals on-farm. In addition, increased awareness of the traceability legislation that exists in Australia to meet the National Performance Standards for Livestock Traceability in this country is required.


Urine dipstick precision with standard visual and automated methods within a small animal teaching hospital.
Urine dipstick results may vary between operators/methods. The magnitude of variation across the veterinary field is currently unknown. The aim of this study was to compare the precision of urine dipstick results between standard direct visual and automated reading methods when performed by several operators. Urine samples were pooled and divided into three aliquots: one plain, one with glucose and one with serum. Final year students, veterinary surgeons and veterinary nurses, blinded to each sample, were then asked to perform dipstick analysis with direct visualisation and an automated analyser, and their technique was observed. A subsequent session was undertaken with samples which had pH titrated to achieve an acidic, neutral or alkaline value. Sixty-four veterinary students, 20 veterinary surgeons and seven veterinary nurses performed the first (n=61) or second (n=30) part of the study. Precision was greater using the automated reader. The most common observed technique errors were: lack of sample mixing, for both visual and automated methods, and not timing readings as per manufacturer instructions when performing visual analysis. This study suggests that in an environment with multiple operators, as is the case in veterinary teaching or large private hospitals, automated urine dipstick reading improves precision of results.


From "retailers" to health care providers: Transforming the role of community pharmacists in chronic disease management.
Community pharmacists are the third largest healthcare professional group in the world after physicians and nurses. Despite their considerable training, community pharmacists are the only health professionals who are not primarily rewarded for delivering health care and hence are under-utilized as public health professionals. An emerging consensus among academics, professional organizations, and policymakers is that community pharmacists, who work outside of hospital settings, should adopt an expanded role in order to contribute to the safe, effective, and efficient use of drugs-particularly when caring for people with multiple chronic conditions. Community pharmacists could help to improve health by reducing drug-related adverse events and promoting better medication adherence, which in turn may help in reducing unnecessary provider visits, hospitalizations, and readmissions while strengthening integrated primary care delivery across the health system. This paper reviews recent strategies to expand the role of community pharmacists in Australia, Canada, England, the Netherlands, Scotland, and the United States. The developments achieved or under way in these countries carry lessons for policymakers world-wide, where progress thus far in expanding the role of community pharmacists has been more limited. Future policies should focus on effectively integrating community pharmacists into primary care; developing a shared vision for different levels of pharmacist services; and devising new incentive mechanisms for improving quality and outcomes.


Illness-related suffering and need for palliative care in Rohingya refugees and caregivers in Bangladesh: A cross-sectional study.
Despite recognition that palliative care is an essential component of any humanitarian response, serious illness-related suffering continues to be pervasive in these settings. There is very limited evidence about the need for palliative care and symptom relief to guide the implementation of programs to alleviate the burden of serious illness-related suffering in these settings. A basic package of essential medications and supplies can provide pain relief and palliative care; however, the practical availability of these items has not been assessed. This study aimed to describe the illness-related suffering and need for palliative care in Rohingya refugees and caregivers in Bangladesh. Between November 20 and 24, 2017, we conducted a cross-sectional study of individuals with serious health problems (n = 156, 53% male) and caregivers (n = 155, 69% female) living in Rohingya refugee camps in Bangladesh, using convenience sampling to recruit participants at the community level (i.e., going house to house to identify eligible individuals). The serious health problems, recent healthcare experiences, need for medications and medical supplies, and basic needs of participants were explored through interviews with trained Rohingya community members, using an interview guide that had been piloted with Rohingya individuals to ensure it reflected the specificities of their refugee experience and culture. The most common diagnoses were significant physical disabilities (n = 100, 64.1%), treatment-resistant tuberculosis (TB) (n = 32, 20.5%), cancer (n = 15, 9.6%), and HIV infection (n = 3, 1.9%). Many individuals with serious health problems were experiencing significant pain (62%, n = 96), and pain treatments were largely ineffective (70%, n = 58). The average age was 44.8 years (range 2-100 years) for those with serious health problems and 34.9 years (range 8-75 years) for caregivers. Caregivers reported providing an average of 13.8 hours of care per day. Sleep difficulties (87.1%, n = 108), lack of appetite (58.1%, n = 72), and lack of pleasure in life (53.2%, n = 66) were the most commonly reported problems related to the caregiving role. The main limitations of this study were the use of convenience sampling and closed-ended interview questioning. In this study we found that many individuals with serious health problems experienced significant physical, emotional, and social suffering due to a lack of access to pain and symptom relief and other essential components of palliative care. Humanitarian responses should develop and incorporate palliative care and symptom relief strategies that address the needs of all people with serious illness-related suffering and their caregivers.


Patient reaction to Tdap vaccination in pregnancy.
The current obstetrical recommendation is to routinely administer the tetanus, diphtheria, and acellular pertussis (Tdap) vaccination during every pregnancy regardless of a patient's prior history. There are minimal data that have prospectively evaluated solicited patient response to this treatment plan. The study objective was to evaluate patient reaction following receipt of Tdap vaccination during pregnancy. This was a prospective observational study conducted from May 2014 through March 2016. The study design involved solicited patient reaction within 1-7days after the administration of the Tdap vaccine. Data collected included pain or soreness, swelling, and/or redness at the injection site, as well as, fever and generalized body aches. Statistical analysis involved simple percentages with Poisson binomial 95% confidence intervals with Chi-square and Fisher's exact comparisons where appropriate. A total of 737 patients were evaluated and 496 (67%, 95% Confidence Interval [CI] 64-71%) were found to have at least 1 reaction to the vaccination and 187 (25%, 95% CI 22-29%) had 2 reactions or more. Overall, the majority of patients stated that the vaccination was tolerated. However, 24 (3%, 95% CI 2-5%) of the study population stated that they would not accept receipt of Tdap in a subsequent pregnancy because of the response that occurred in the current pregnancy. These data demonstrate that maternal reactions following receipt of Tdap are common (two-thirds of the study population). A potential concern is the finding that some patients might refuse a repeat vaccination in a subsequent pregnancy due to these reactions. If further research reveals similar findings, a pertussis only vaccine for pregnant patients might need to be evaluated.